Interferon-gamma regulation of B lymphocyte differentiation: activation of B cells is a prerequisite for IFN-gamma-mediated inhibition of B cell differentiation

Abstract

The Th1 and NK cell-derived cytokine interferon-gamma (IFN-gamma) influences both immune and inflammatory responses, and under some circumstances, IFN-gamma can inhibit B cell differentiation. We found that IFN-gamma inhibited LPS-induced IgM production in B cells by reducing the precursor frequency of IgM-secreting cells. This occurred without a significant decrease in B cell proliferation in response to either LPS or F(ab')2 anti-IgM. We also found that IFN-gamma inhibited IgM secretion, even when added as late as 48 hr after LPS stimulation. Small resting B cells were not affected by a pulse with IFN-gamma. However, a pulse of IFN-gamma inhibited the response of activated B cells to subsequent stimulation with LPS. Also, LPS upregulated expression of the IFN-gamma receptor on B cells. Our studies show that IFN-gamma targets stimulated but not resting B cells and suggest that IFN-gamma plays an important role in the normal homeostatic control of B cell polyclonal responses.